P1025: A PILOT STUDY OF THE ANTI-SLAMF7 MONOCLONAL ANTIBODY, ELOTUZUMAB, IN PATIENTS WITH MYELOFIBROSIS.
Authors: Prithviraj Bose, Lucia Masarova, Naveen Pemmaraju, Mackenzie Dobbins, Nitin Jain, Hussein Abbas, Steven Kornblau, Abhishek Maiti, Ivo Veletic, Taghi Manshouri, Sharon Bledsoe, Mary Ann Richie, Nakiuda Hall-Moore, Lingsha Zhou, Xuemei Wang, Hagop Kantarjian, Zeev Estrov, Srdan Verstovsek
Journal: HemaSphere (2023)

Topic: 16. Myeloproliferative neoplasms - Clinical Background: Thrombopoietin receptor (MPL) activation induces fibrocyte differentiation and blood monocytes highly expressing MPL and signaling lymphocyte activation molecule family member 7 (SLAMF7) are possible fibrocyte precursors (Maekawa, Leukemia 2018). Elotuzumab (Elo), a SLAMF7-targeting monoclonal antibody, inhibited the differentiation of MF patient-derived fibrocytes in vitro and romiplostim-induced bone marrow (BM) fibrosis and splenomegaly in vivo (Maekawa, Blood 2019). Aims: To explore the efficacy and safety of Elo in patients with myelofibrosis (MF). Methods: This is a single-institution, investigator-initiated, pilot phase 2 study (NCT04517851) of Elo in patients (pts) with primary or post-polycythemia vera/essential thrombocythemia MF who are not candidates for JAK inhibitor (JAKi) therapy (prior JAKi permitted). Elo is dosed intravenously weekly at 10 mg/kg/w for the first 8 w, followed by 20 mg/kg q4w, and continued until disease progression or unacceptable toxicity (max 36 cycles). Spleen and liver sizes are measured by palpation and the MPN-SAF-TSS questionnaire (Emanuel, J Clin Oncol 2012) is administered on day 1 of each cycle. Pts receive a BM biopsy at screening and every 6 cycles on-study. Plasma cytokines are measured at baseline and every 3 cycles on-study. Responses are adjudicated by the revised IWG-MRT-ELN criteria (Tefferi, Blood 2013) and must last ≥12 w. In pts with baseline (BL) plts <100 x 109/L, major, intermediate and minor plt responses are defined as ≥75%, 50-74% and 25-49% increases from BL. Elo is provided by Bristol-Myers Squibb. Extensive correlative studies are in progress. Results: Eleven pts had been treated as of the data cutoff date (Feb 14, 2023). BL characteristics appear in the Table. One pt had returned to chronic phase primary MF at study entry after successful treatment for transformation to acute myeloid leukemia (AML). Six pts continue on-study; reasons for discontinuation include lack of response in 3 pts, transformation to AML in 1 pt, and death from unrelated medical complications in 1 pt. Ten pts have completed the initial weekly dosing phase. Two pts experienced clinical improvement (CI) in symptoms (sx) lasting 11.9 and 7.4 m, respectively; the first pt (now deceased from a GI bleed) also had a major plt response that lasted 15.3 m. This pt also experienced a decrease in erythrocyte transfusion frequency, but not transfusion independence (TI). Times to response for the 2 CI-sx responses were 3.7 and 0.9 m, respectively. Time to the plt response was 0.3 m. An additional pt had a TI response lasting 12 w, but subsequently lost it. Two other pts have had ≥2 g/dL improvements in Hgb; one subsequently came off-study and one remains on-study. One pt had improvement in BM fibrosis grade from MF-3 to MF-2 after 2.8 m and continues on-study. One pt experienced disease progression to AML and was taken off-study. Elo was very well-tolerated. One pt each experienced grade 1 headache, grade 1 hyperglycemia, grade 2 infusion reaction (chills) and grade 3 diarrhea felt to be possibly related to elo. There were 3 deaths on-study, all unrelated to elo: one from GI hemorrhage, one due to pneumonia/multi-organ failure and one from infection at an outside hospital (details unknown). Updated clinical results, as well as results from correlative studies, will be presented. Summary/Conclusion: Elo is active in the treatment of MF and has an excellent safety profile. A total of 15 pts are planned to be accrued to this pilot study. Future studies in combination with JAKi therapy appear warranted.Keywords: Idiopathic myelofibrosis, Targeted therapy, Myelofibrosis, Myeloproliferative disorder